A contributing factor to the development of arthritis is the inappropriate proteolytic destruction of the aggrecan component of cartilage by the proteolytic enzyme aggrecanase. The immune system signal molecule interleukin 2 (IL-2) activates aggrecanase; in fact, IL-2 blockers are sometimes used to treat arthritis. Studies were undertaken to determine whether inhibitors of aggrecanase could counteract the effects of IL-2. Pieces of cartilage were incubated in media with various additions and the amount of aggrecan destruction was measured as a function of time. Aggrecan degradation was measured by the release of glycosaminoglycan. What is the rationale for this assay? Aggrecan is a transferase enzyme that adds glycosaminoglycans to glycoproteins, and these glycosaminoglycans remain free if aggrecan is degraded. Aggrecan is a lectin that binds glycosaminoglycan ligands, and aggrecan releases these glycosaminoglycans as it is degraded. Aggrecan inhibits the removal of glycosaminoglycans from proteoglycans, and aggrecan degradation allows this removal to proceed. O Aggrecan is heavily decorated with glycosaminoglycans, and the release of these glycosaminoglycans is a sign of aggrecan degradation.

Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
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**Topic: Aggrecan Degradation and Arthritis**

A significant factor in the development of arthritis is the inappropriate proteolytic destruction of the aggrecan component of cartilage by the enzyme aggrecanase. The immune system molecule interleukin 2 (IL-2) activates aggrecanase; IL-2 blockers are sometimes used in arthritis treatment.

**Research Context:**

Studies have been conducted to explore whether inhibitors of aggrecanase could counteract the effects of IL-2. During these studies, cartilage pieces were incubated in media with various additives, and the extent of aggrecan destruction was measured over time.

**Measurement Method:**

Aggrecan degradation was monitored by the release of glycosaminoglycan. This method is based on the following rationale:

- **Options for Understanding the Rationale:**
  - Aggrecan is a transferase enzyme that adds glycosaminoglycans to glycoproteins, which remain free if aggrecan is degraded.
  - Aggrecan acts as a lectin binding to glycosaminoglycan ligands, releasing them upon degradation.
  - Aggrecan inhibits the removal of glycosaminoglycans from proteoglycans, and its degradation allows for this removal.
  - Aggrecan is heavily decorated with glycosaminoglycans, and their release indicates aggrecan degradation.

Choosing the correct rationale helps in understanding how aggrecanase activity relates to cartilage integrity and the potential effectiveness of IL-2 inhibitors in therapeutic interventions.
Transcribed Image Text:**Topic: Aggrecan Degradation and Arthritis** A significant factor in the development of arthritis is the inappropriate proteolytic destruction of the aggrecan component of cartilage by the enzyme aggrecanase. The immune system molecule interleukin 2 (IL-2) activates aggrecanase; IL-2 blockers are sometimes used in arthritis treatment. **Research Context:** Studies have been conducted to explore whether inhibitors of aggrecanase could counteract the effects of IL-2. During these studies, cartilage pieces were incubated in media with various additives, and the extent of aggrecan destruction was measured over time. **Measurement Method:** Aggrecan degradation was monitored by the release of glycosaminoglycan. This method is based on the following rationale: - **Options for Understanding the Rationale:** - Aggrecan is a transferase enzyme that adds glycosaminoglycans to glycoproteins, which remain free if aggrecan is degraded. - Aggrecan acts as a lectin binding to glycosaminoglycan ligands, releasing them upon degradation. - Aggrecan inhibits the removal of glycosaminoglycans from proteoglycans, and its degradation allows for this removal. - Aggrecan is heavily decorated with glycosaminoglycans, and their release indicates aggrecan degradation. Choosing the correct rationale helps in understanding how aggrecanase activity relates to cartilage integrity and the potential effectiveness of IL-2 inhibitors in therapeutic interventions.
**Educational Content on Glycosaminoglycan Release and Aggrecan Degradation**

**Understanding the Question:**
The question being addressed is: Why might glycosaminoglycan release not indicate aggrecan degradation?

**Multiple Choice Answers:**

1. **Option 1:** Glycosaminoglycans are hydrogen bonded to aggrecan and may dissociate from aggrecan at high temperatures.

2. **Option 2:** Another enzyme might be present that cleaves glycosaminoglycans from aggrecan without degrading aggrecan.

3. **Option 3:** Glycosaminoglycan release also occurs with the degradation of glycogen in animal tissues.

4. **Option 4:** Aggrecanase may degrade the glycosaminoglycans of aggrecan without degrading the protein component.

Each option provides a possible explanation for the observation that glycosaminoglycan release does not necessarily imply the degradation of aggrecan. Understanding these options requires a basic knowledge of biochemistry, particularly the behavior of enzymes and molecular bonds.
Transcribed Image Text:**Educational Content on Glycosaminoglycan Release and Aggrecan Degradation** **Understanding the Question:** The question being addressed is: Why might glycosaminoglycan release not indicate aggrecan degradation? **Multiple Choice Answers:** 1. **Option 1:** Glycosaminoglycans are hydrogen bonded to aggrecan and may dissociate from aggrecan at high temperatures. 2. **Option 2:** Another enzyme might be present that cleaves glycosaminoglycans from aggrecan without degrading aggrecan. 3. **Option 3:** Glycosaminoglycan release also occurs with the degradation of glycogen in animal tissues. 4. **Option 4:** Aggrecanase may degrade the glycosaminoglycans of aggrecan without degrading the protein component. Each option provides a possible explanation for the observation that glycosaminoglycan release does not necessarily imply the degradation of aggrecan. Understanding these options requires a basic knowledge of biochemistry, particularly the behavior of enzymes and molecular bonds.
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